Microinjection of the dopamine antagonist cis-flupenthixol into the MPOA impairs copulation, penile reflexes and sexual motivation in male rats

Microinjection of the dopamine antagonist cis-flupenthixol into the medial preoptic area was previously shown to impair male rat copulatory behavior. The present experiments provide further evidence of cis-flupenthixol's inhibitory effects on male sexual behavior. Following microinjections of moderate to high doses of cis-flupenthixol, males exhibited slower copulatory rates and fewer ejaculations in copula, fewer ex copula erections and penile movements, and reduced sexual motivation in an X-maze. Locomotion in the X-maze was not significantly affected. Microinjections of the inactive isomer trans-flupenthixol produced no change in any behavioral measure, indicating that cis-flupenthixol's effects were receptor mediated. We suggest that dopamine receptors in the MPOA influence copulation primarily by regulating reflexive and motivational factors, but not locomotion.     

Dopamine receptors in the ventral tegmental area affect motor, but not motivational or reflexive, components of copulation in male rats

Microinjection of apomorphine into the ventral tegmental area (VTA) of male rats was previously shown to delay the onset of copulation and slow its rate, presumably by stimulating impulse-regulating autoreceptors on cell bodies of the A10 mesocorticolimbic dopamine tract. Such stimulation would be expected to slow the firing rate of these neurons and, thereby, to impair locomotion and/or motivational processes. The present experiments tested whether the delayed onset and slowed rate of copulation were related to deficits in motor performance, sexual motivation, and/or genital reflexes. In X-maze tests the speed of running to all 4 goal boxes was slowed; however, the percentage of trials on which the male chose the female's goal box was not decreased. Examination of videotaped copulation tests revealed that the male showed fewer complete copulatory behaviors (mounts, intromissions, and ejaculations), but more misdirected or incomplete copulatory attempts after apomorphine in the VTA. There were also fewer scores of active, as opposed to inactive, behaviors, and the onset and rate of copulation were slowed. The total number of female directed behaviors was not different in apomorphine tests, compared to vehicle. Finally, tests of ex copula genital reflexes revealed no significant effects of apomorphine in the VTA on erections, penile movements, or seminal emissions. These data suggest a role of the VTA in the motor aspects and/or sensorimotor integration of copulation. Sexual motivation and ex copula genital reflexes appeared to be unaffected by apomorphine in the VTA.     

Differential effects of the antiandrogen flutamide on aspects of sexual behavior in castrated, androgen-treated male rats

(1) This study focused on the question of whether the behavioral effects of the non-steroidal antiandrogen flutamide result from actions on CNS or peripheral mechanisms governing sexual behavior in male rats. (2) Restoration of sexual behavior in long-term male castrates was evaluated in response to administration of testosterone propionate (TP) with or without flutamide. (3) Two types of behavioral tests were employed—one was a standard test of the complete copulatory behavior pattern while the other involved anesthetization of the male's penis which served to reduce the role of peripheral factors in the male's behavior and eliminate intromission and ejaculatory behavior. (4) In the behavioral tests with genital anesthetization, flutamide facilitated mounting behavior. (5) Since mounting behavior in these tests presumably represents CNS function, facilitation of the behavior indicates that flutamide acts as an androgen, and not as an antindrogen, on CNS mechanisms. (6) In the behavioral complete copulatory behavior pattern, flutamide inhibited ejaculation and, to a lesser extent, intromission behavior. (7) Flutamide also completely inhibited the stimulatory effect of TP on peripheral structures. (8) It was concluded that the inhibitory effect of flutamide on ejaculation behavior resulted from deficiencies in peripheral, especially penile, structures although an alternative possibility—that flutamide differentially affects two CNS mechanisms governing mounting and ejaculation—cannot be excluded.     

Modification of sexual behavior of Long-Evans male rats by drugs acting on the 5-HT1A receptor

Modulation of the sexual behavior of male rats by the anxiolytic buspirone (S-20499) and its analog gepirone were compared to the effects of 8-OH-DPAT (or DPAT, a selective 5-HT1A reference agonist), and BMY-7378 (a selective 5-HT1A partial agonist). Long-Evans rats were used; modulation of copulatory behavior and alteration of penile reflexes were examined. Modulation of copulatory behavior was assessed by three indices: frequency and length of intromission, and latency of ejaculation. DPAT, at doses of 1-8 mg/kg, reduced these three indices in a time dependent manner such that the effects peaked at 45 min and normalized at 90 min. The dose-effect relationship (assessed 45 min after DPAT injection) is bell-shaped with an ED50 approximately 1 mg/kg on the ascending limb of the curve. The effects of buspirone (2 mg/kg) and gepirone (2 mg/kg) on copulatory behavior were indistinguishable from control. BMY-7378 alone and in combination with these other 5-HT1A agonists reduced copulatory behavior, though not statistically significant. Penile reflexes, including number of erections, cups and flips, were inhibited by these agents: DPAT>buspirone>gepirone (inactive at 2 mg/kg). Furthermore, the latency period to erection was at least doubled by DPAT (2 mg/kg). Buspirone and gepirone, however, reduced the latency period to erection. BMY-7378 inhibited penile reflexes when administered alone and even more in combination with DPAT or buspirone. Two butyrophenone analogs, spiperone (a 5-HT1A and dopamine D2 antagonist) and haloperidol (a D2 antagonist), were also tested for their interaction with DPAT. Both of these drugs (at 0.25 mg/kg, 60 min after administration) reduced all indices of penile reflexes and copulation. Furthermore, in combination with DPAT (2 mg/kg, 45 min), the effects were synergistic such that sexual activity came nearly to a standstill. These opposing effects on putatively brain originated copulatory behavior and spinal mediated penile reflexes indicate that the effects of buspirone and DPAT on sexual behavior in the male rat may be possible at different parts of the central nervous system. If a tentative shared target site by DPAT and buspirone is the 5-HT1A receptor, than the same 5-HT receptor sub-type at different locations (brain, raphe nuclei, spinal cord and autonomic ganglia) may modulate rat sexual behavior in opposing ways.     

Microinjection of cis-flupenthixol, a dopamine antagonist, into the medial preoptic area impairs sexual behavior of male rats

Systematically administered dopamine agonists have been shown to facilitate copulation in male rats. Microinjection of the dopamine agonist apomorphine into the medial preoptic area has also been reported to facilitate sexual behavior. The present experiments investigated the effects of medial preoptic microinjections of the dopamine antagonist cis-flupenthixol on male rat copulatory behavior. Fewer males initiated copulation and fewer ejaculated following flupenthixol administration. Those males that did ejaculate following flupenthixol injections had fewer ejaculations and longer interintromission intervals. Flupenthixol also antagonized the facilitative effects of apomorphine injections into the medial preoptic area. Flupenthixol and apomorphine produced only minor alterations in non-copulatory behaviors. The results suggest that dopamine receptors within the medial preoptic area are important in the regulation of masculine sexual behavior in the rat.     

Perineal striated muscles: Anatomy, spinal motoneurons, and participation on copulatory behavior in male rabbits (Oryctolagus cuniculus)

Despite the importance of rabbits in reproductive studies, little information is available on the anatomy and participation of the striated-perineal muscles in male copulatory behavior. In our study, we describe the gross anatomy of two striated-perineal muscles: the ischiocavernosus (ICm) and the bulbospongiosus (BSm). Both muscles have their origin at the ischiadic arc, but the ICm is inserted into the penile crura and the BSm onto the ligamentum suspensorium of the penis. The motoneurons of both muscles were identified using retrograde labeling with horseradish peroxidase coupled to wheat-germ agglutinin. Motoneurons were dispersed in the lower-lumbar and upper-sacral spinal-cord segments, instead of being aggregated in the neuronal nucleus as in other species: the rat, mouse, gerbil, cat, and man. Bilateral dennervation of the ICm or BSm or both in sexually experienced male rabbits did not affect copulatory variables measured at 10, 20, and 30 days after surgery. However, muscular dennervation produced extravaginal ejaculations in 42% of copulatory tests and no ejaculation in 7% of tests, although male pelvic thrusting occurred. These results suggest the participation of the ICm and BSm perineal muscles in penile orientation during copulation but not in seminal emission as described in other mammalian species.     

Pubertal development of penile reflexes and copulation in male rats

(1) Three groups of male rats were tested from 25 to 55 days of age for copulatory behavior, penile reflexes, or plasma testosterone (T). (2) Penile reflexes and copulatory behavior developed prior to the time of maximum T, but not before T had reached appreciable levels. (3) Penile reflex potential developed concurrently with copulation: the ages at which mounts, intromissions, and ejaculations first appeared were matched by the ages of appearance of penile erections, flips and cups respectively. (4) Of the behavioral measures, only penile cups and the ejaculatory pattern did not appear before preputial separation. (5) To the extent that laboratory rats are unique in having parallel development of copulatory behavior and penile reflexes, their value as a mammalian model of behavioral puberty is restricted.     

Hormone-neurotransmitter interactions in the control of sexual behavior.

The stimuli from a receptive female and/or copulation itself leads to the release of dopamine (DA) in at least three integrative hubs. The nigrostriatal system promotes somatomotor activity; the mesolimbic system subserves numerous types of motivation; and the medial preoptic area (MPOA) focuses the motivation onto specifically sexual targets, increases copulatory rate and efficiency, and coordinates genital reflexes. The previous (but not necessarily concurrent) presence of testosterone is permissive for DA release in the MPOA, both during basal conditions and in response to a female. One means by which testosterone may increase DA release is by upregulating nitric oxide synthase, which produces nitric oxide, which in turn increases DA release. Hormonal priming in females may also increase DA release in the MPOA, and copulatory activity may further increase DA levels in females. One of the intracellular effects of stimulation of DA D1 receptors in the MPOA of male rats may be increased expression of the immediate-early gene c-fos, which may mediate longer term responses to copulation. Furthermore, increased sexual experience led to increased immunoreactivity to Fos, the protein product of c-fos, following copulation to one ejaculation. Another intracellular mediator of DA's effects, particularly in castrates, may be the phosphorylation of steroid receptors. Finally, while DA is facilitative to copulation, 5-HT is generally inhibitory. 5-HT is released in the LHA, but not in the MPOA, at the time of ejaculation. Increasing 5-HT in the LHA by microinjection of a selective serotonin reuptake inhibitor (SSRI) increased the latency to begin copulating and also the latency to the first ejaculation, measured from the time the male first intromitted. These data may at least partially explain the decrease in libido and the anorgasmia of people taking SSRI antidepressants. One means by which LHA 5-HT decreases sexual motivation (i.e. increases the latency to begin copulating) may be by decreasing DA release in the NAcc, a major terminal of the mesolimbic system. Thus, reciprocal changes in DA and 5-HT release in different areas of the brain may promote copulation and sexual satiety, respectively.     

Sexual performance and precontact 50-kHz ultrasonic vocalizations in WAG/Rij rats: Effects of opioid receptor treatment

WAG/Rij rats are genetically selected animals that model absence epilepsy in rats. Ultrasonic vocalizations and sexual behavior – both ethologically relevant markers of reward system functioning – are poorly described in this strain. The aim of our experiment was to investigate reward-dependent precontact 50-kHz vocalizations (PVs) and copulatory behavior as well as the effects of opioid receptor treatment on such behaviors in sexually experienced WAG/Rij males and rats from two control strains: Sprague–Dawley and Crl: Han Wistar. We analyzed the effects of the opioid receptor antagonist naltrexone (3 mg/kg) and the agonist morphine (1 mg/kg) administration. Additionally, we analyzed the initiation of copulation in sexually naïve males before drug treatment. A significantly lower number of sexually naïve WAG/Rij rats initiated copulation. Sexually experienced WAG/Rij males differed at the control session (after physiological saline treatment) compared with Sprague–Dawley rats: WAG/Rij rats displayed more 50-kHz precontact vocalizations and had longer mount and intromission latencies, longer ejaculation latency, longer postejaculatory latency to exploration, longer 22-kHz vocalization duration after ejaculation, and longer postejaculatory intromission latency. Compared with Crl: Han Wistar rats, WAG/Rij males displayed longer mount latency and shorter 22-kHz vocalization duration. Neither naltrexone nor morphine affected PVs in all groups. On the other hand, opioid receptor treatment differently influenced the number of intromissions required to achieve ejaculation and 22-kHz postejaculatory vocalization duration in WAG/Rij rats than in both control groups. This suggests functional differences in the opioid system in this strain. As a result of the number of males that initiated copulation as well as the number of intromissions to ejaculation and 22-kHz postejaculatory vocalizations which all depend on D1 receptor activation, we suggest that the proportion of opioid receptor to D1 receptors in WAG/Rij rats is different when compared with the control strains. The reward system of Wag/Rij rats with absence epilepsy is sensitive to social rewards (high level of precontact 50-kHz ultrasounds) although this strain displays a lower level of sexual motivation (longer mount latency) compared with other control strains. A lower number of sexually naïve rats initiating copulation and longer mount latency in sexually experienced males could suggest a moderate depressive-like syndrome in this strain of rats.     

Preoptic knife cuts and sexual behavior in male rats

Knife cuts aimed at severing either the medial-lateral or dorsal fiber connections of the medial preoptic-anterior hypothalamus (MPOAH) produced two clearly distinguishable patterns of copulatory deficits in male rats. On the other hand, transverse cuts, which were designed to destroy longitudinal connections on either the anterior or posterior end of the MPOAH, did not affect sexual behavior. Males with sagittal cuts exhibited deficits primarily in the initiation of copulation. In contrast, those with dorsal cuts showed alterations primarily in the execution of copulatory behavior. Combined behavioral and anatomical evidence was interpreted as suggesting that the MOPAH has at least two regulatory functions related to sex behavior: (1) it is involved in the mediation of the initiation of copulation through its lateral connections with the medial forebrain bundle, and (2) it influences the achievement of ejaculation and the subsequent refractory period through its dorsal connections with the amygdala and the hippocampus.